Many patients die of liver failure such as chronic liver failure including liver cirrhosis and acute liver failure every year. As a radical treatment for these diseases, liver transplantation is presently carried out. Since the liver transplantation is a highly invasive treatment, a safer treatment, hepatocyte transplantation, has been proposed. However, the hepatocyte transplantation requires a large amount of cells at a time. Because of this, deficiency in donors is concerned.
Development of pharmaceutical candidate compounds is terminated mainly due to “hepatotoxicity”. Thus, in development of pharmaceutical products, the toxicity is evaluated by using a human hepatocyte primary culture, in vitro. However, it is difficult to stably supply the hepatocyte primary culture with lot-to-lot uniformity and thus stable inspection results are not obtained.
Then, for transplantation and search for pharmaceutical products, producing hepatocytes from pluripotent stem cells such as embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells) has attracted attention. Up to present, a number of methods of producing hepatocytes from pluripotent stem cells have been reported (Patent Literature 1, Non Patent Literature 1, Non Patent Literature 2, Non Patent Literature 3). In the methods reported, proteins such as HGF and oncostatin M are employed for efficient maturation into hepatocytes. However, if such a protein is used, cost for cell induction increases and efficiency varies depending upon lot-to-lot variation of the protein. We occasionally come across such problems.